In most healthy individuals, the maintenance of blood glucose is a carefully regulated metabolic event. Glucagon, the 29-amino acid peptide responsible for maintaining blood glucose levels, increases glucose release from the liver by activating hepatic glycogenolysis and gluconeogenesis. When elevated blood glucose levels are present in an individual, insulin reverses the glucagon-mediated enhancement of glycogenolysis and gluconeogenesis. In some individuals, however, elevated glucose levels detrimentally persist for extended periods.
Such elevated glucose levels are most often associated with diabetes mellitus, a disease characterized by elevated glucose levels resulting from either an inability to produce insulin (Type I diabetes) or insulin resistance, i.e., the produced insulin is not sufficiently active in the individual (Type II diabetes) such that a given concentration of insulin produces a less-than-expected biological effect.
The key to diabetes treatment is to control circulating blood glucose levels within generally acceptable limits. Thus, diabetes treatment has traditionally focused on increasing insulin levels by injection, or alternatively, using oral agents to control blood glucose levels. Oral agents capable of controlling blood glucose levels include over-the-counter medications (e.g., metformin) and compositions derived from natural products, for example, compositions comprising plant extracts.
Type II diabetes (or non-insulin dependent diabetes) is often accompanied by metabolic syndrome. Metabolic syndrome is not a disease state per se, but rather the collective presence in an individual of risk factors such as abdominal obesity, atherogenic dyslipidemia, raised blood pressure, insulin resistance, glucose intolerance, proinflammatory conditions, and prothrombotic conditions [Grundy, et al., Circulation, 109(3):433-8 (2004)]. When one or more (particularly, three or more) of such risk factors is present, the individual has an increased risk for a variety of disease states including diabetes, heart disease, and/or stroke. Individuals having metabolic syndrome are also susceptible to other conditions such as polycystic ovary syndrome, fatty liver, cholesterol gallstones, asthma, sleep disturbances, and some forms of cancer. Thus, individuals suffering from type II diabetes are often obese and/or susceptible to hypertension (cardiovascular problems), in addition to having insulin resistance and/or elevated glucose levels.
Elevated glucose levels can also be present in individuals who are considered to have “pre-diabetes,” a condition in which an individual's blood glucose levels are elevated, but not as much as individuals having diabetes.
Glucose levels are generally determined by using a Fasting Plasma Glucose Test (FPG) or an Oral Glucose Tolerance Test (OGTT), but other tests may also be used. With the FPG test, a fasting blood glucose level between 100 and 125 milligrams per deciliter (mg/dL) is indicative of pre-diabetes, and a fasting blood glucose level of 126 mg/dL or higher is indicative of diabetes. With the OGTT test, an individual's blood glucose level is measured two hours after drinking a glucose-rich beverage. A two-hour blood glucose level between 140 and 199 mg/dL is indicative of pre-diabetes, and a two-hour blood glucose level at 200 mg/dL or higher is indicative of diabetes.
Studies demonstrate that several biochemical pathways associated with elevated glucose levels can increase the production of free radicals [Giugliano, et al., Diabetes Care, 19:257-67 (1996)]. Free radicals generated by the autoxidation reactions of sugar and sugar adducts to proteins are possible sources of oxidative stress in patients with elevated glucose levels. Further, glycoxidation products accumulate in tissue collagen at an accelerated rate in patients with elevated glucose levels [Baynes, Diabetes, 40:405-12 (1991)]. Oxidative stress leads to complications including tissue damage and cell death. Thus, individuals having such elevated glucose levels have increased risks for heart disease (cardiovascular disease), blindness (retinopathy), nerve damage (neuropathy), kidney damage (nephropathy), and other conditions. In view of the foregoing, compositions that lower glucose levels are significant for health and wellness in general.